Background/Purpose:

Systemic sclerosis (SSc) is a heterogeneous disorder characterized by excessive fibrosis and microvascular damage of the skin and various internal organs. Cutaneous mononuclear cell infiltrates in early SSc skin lesions are mostly activated T cells which are also increased in lung interstitium and bronchoalveolar fluid from patients with SSc and active interstitial lung disease. Furthermore, cytokines or growth factors regulate SSc induction by stimulating the synthesis of extracellular matrix components, which may injure endothelial cells and modulate leukocyte function. These infiltrating activated T cells are likely to release cytokines, chemokines, or growth factors, which play a crucial part in the initiation and development of fibrosis in SSc.

            Inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is expressed in activated T cells, but not in naïve T cells. ICOS specifically binds to ICOS ligand (ICOSL), which is constitutively expressed on antigen-presenting cells such as B cells and macrophages. ICOS-mediated costimulation is crucial for T cell proliferation, production of various cytokines, and T cell-dependent B cell responses. ICOS–ICOSL interaction is likely to contribute to the development of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Therefore, we suggest that ICOS plays a role in the pathogenesis of SSc and, in this study, examined serum soluble ICOS (sICOS) levels in SSc patients, and evaluated the results with respect to clinical features.

Methods:

Serum sICOS levels were examined by enzyme-linked immunosorbent assay in 38 patients with SSc, and 24 healthy individuals. In addition, the expression of ICOS and ICOSL in skin was examined immunohistochemically.

Results:

Patients with diffuse cutaneous SSc had higher levels of sICOS than those with limited cutaneous SSc or healthy individuals. Serum sICOS levels correlated positively with the severity of skin sclerosis. Patients with SSc and elevated sICOS levels more often had interstitial lung disease and decreased vital capacity than those with normal sICOS levels. The serum sICOS levels were significantly greater in patients with early phase SSc than those with late-phase SSc. ICOS and ICOSL immunostaining was observed on infiltrating dermal mononuclear cells in lesional skin tissue.

Conclusion:

The current study suggests that ICOS may contribute to the development of SSc. Given that no therapy has proven effective in suppressing or improving skin sclerosis and interstitial lung disease in SSc to date, our findings suggest that ICOS inhibition could be a potential treatment for patients with SSc who have severe skin sclerosis and interstitial lung disease. In addition, measurement of serum sICOS levels in patients with early SSc may offer an important means for further evaluation of SSc disease severity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-possible-contribution-of-inducible-costimulator-to-the-development-of-skin-sclerosis-and-interstitial-lung-disease-in-systemic-sclerosis/